This is an application for a Research Career Development Award designed to promote the development of Dr. Shannon Kenney's independent research career. Dr. Kenney's research interests have focused around the regulatory proteins of the Epstein-Barr virus (EBV). In previous work in her laboratory she has investigated the mechanisms whereby the EBV immediate-early (IE) proteins control EBV replication. In addition, an ongoing interest of her laboratory has been the ability of these EBV-encoded proteins to regulate important cellular and HIV genes. The particular project in this grant application investigates the mechanism(s) whereby the EBV BRLF1 IE protein activates c-myc expression. The possibility that BRLFl-induced activation of c-myc is important in the development of AMS-related lymphomas is suggested by A) the high frequency of EBV-positive lymphomas in AIDS patients, B) the expression of replicative EBV functions in these lymphomas, and C) the previously demonstrated ability-of activated c-myc to synergistically with EBV-encoded transforming functions.